Tag: pubmed

Brain. 2025 May 6:awaf172. doi: 10.1093/brain/awaf172. Online ahead of print.

ABSTRACT

Migraine has an assumed polygenic basis, but the genetic risk variants identified in genome-wide association studies only explain a proportion of the heritability. We aimed to develop machine learning models, capturing non-additive and interactive effects, to address the missing heritability. This was a cross-sectional population-based study of participants in the second and third Trøndelag Health Study. Individuals underwent genome-wide genotyping and were phenotyped based on validated modified criteria of the International Classification of Headache Disorders. Four datasets of increasing number of genetic variants were created using different thresholds of linkage disequilibrium and univariate genome-wide associated p-values. A series of machine learning and deep learning methods were optimized and evaluated. The genotype tools PLINK and LDPred2 were used for polygenic risk scoring. Models were trained on a partition of the dataset and tested in a hold-out set. The area under the receiver operating characteristics curve was used as the primary scoring metric. Classification by machine learning was statistically compared to that of polygenic risk scoring. Finally, we explored the biological functions of the variants unique to the machine learning approach. 43,197 individuals (51% women), with a mean age of 54.6 years, were included in the modelling. A light gradient boosting machine performed best for the three smallest datasets (108, 7,771 and 7,840 variants), all with hold-out test set area under curve at 0.63. A multinomial naïve Bayes model performed best in the largest dataset (140,467 variants) with a hold-out test set area under curve of 0.62. The models were statistically significantly superior to polygenic risk scoring (area under curve 0.52 to 0.59) for all the datasets (p<0.001 to p=0.02). Machine learning identified many of the same genes and pathways identified in genome-wide association studies, but also several unique pathways, mainly related to signal transduction and neurological function. Interestingly, pathways related to botulinum toxins, and pathways related to the calcitonin gene-related peptide receptor also emerged. This study suggests that migraine may follow a non-additive and interactive genetic causal structure, potentially best captured by complex machine learning models. Such structure may be concealed where the data dimensionality (high number of genetic variants) is insufficiently supported by the scale of available data, leaving a misleading impression of purely additive effects. Future machine learning models using substantially larger sample sizes could harness both the additive and the interactive effects, enhancing precision and offering deeper understanding of genetic interactions underlying migraine.

PMID:40326299 | DOI:10.1093/brain/awaf172

J Clin Hypertens (Greenwich). 2025 May;27(5):e70053. doi: 10.1111/jch.70053.

ABSTRACT

Screenings for hypertension, diabetes, and high cholesterol are widely conducted in routine clinical practice for cardiovascular disease (CVD) prevention. However, few studies have investigated whether these screenings could eventually lead to lower risks of hard outcomes such as mortality. This cohort study aimed to examine directly the association of screenings for hypertension, diabetes, and high cholesterol with all-cause and cardiovascular mortality and whether the association, if existent, varied with important characteristics. A nationally representative sample of 86 587 US adults without the three conditions and CVD at baseline were recruited. The history of screenings for the three conditions was elicited by a series of questions in the surveys. All-cause and cardiovascular mortality were ascertained by linkage to National Death Index records through December 31, 2019. The association of screenings with mortality was investigated by multivariable Cox regression analysis and expressed as hazard ratio (HR) with 95% confidence interval (CI), adjusting for major risk factors of CVD and mortality. The “1 screening,” “2 screenings,” “3 screenings,” and “any screening” (combining the above three) groups were compared with the “no screening” group separately. During a median follow-up of 51 months (4.3 years), 1783 participants died and 366 of them were attributed to CVD. After adjusting for all covariates, no statistically significant association was found between “any screening” and all-cause mortality (HR = 1.08, 95% CI 0.92-1.26) or cardiovascular mortality (HR = 1.06, 95% CI 0.76-1.47). The results were consistent across various subgroups. The associations of “1 screening,” “2 screenings,” and “3 screenings” respectively with all-cause and cardiovascular mortality were not statistically significant either (HRs ranging from 0.65 to 1.40). Overall, in this population of US general adults, there was no evidence that screening for hypertension, diabetes, and high cholesterol could lead to lower all-cause or cardiovascular mortality.

PMID:40326297 | DOI:10.1111/jch.70053

Genome Biol Evol. 2025 May 6:evaf080. doi: 10.1093/gbe/evaf080. Online ahead of print.

ABSTRACT

Population branch statistics, which estimate the degree of genetic differentiation along a focal population’s lineage, have been used as an alternative to FST-based genome-wide scans for identifying loci associated with local selective sweeps. Beyond the population branch statistic (PBS), the normalized PBSn1 adjusts focal branch length with respect to outgroup branch lengths at the same locus, whereas population branch excess (PBE) incorporates median branch lengths at other loci. PBSn1 and PBE were proposed to be more specific to local selective sweeps as opposed to geographically ubiquitous selection. However, the accuracy and statistical power of branch statistics have not been systematically assessed. To do so, we simulate genomes in representative large and small populations with varying proportions of sites evolving under genetic drift or (approximated) background selection, with local selective sweeps or geographically parallel selective sweeps. We then assess the probability that local selective sweep loci are correctly identified as outliers by FST and by each of the branch statistics. We find that branch statistics consistently outperform FST at identifying local sweeps. Particularly when parallel sweeps are introduced, PBSn1 and PBE correctly identify local sweeps among their top outliers more frequently than PBS. Additionally, we evaluate versions of these statistics based on maximal site differentiation within a window, finding that site-based PBE and PBSn1 are particularly effective at identifying local soft sweeps. These results validate the greater specificity of the rescaled branch statistics PBE and PBSn1 to detect population-specific positive selection, supporting their use in genomic studies focused on local adaptation.

PMID:40326284 | DOI:10.1093/gbe/evaf080

Int J Soc Psychiatry. 2025 May 6:207640251336725. doi: 10.1177/00207640251336725. Online ahead of print.

ABSTRACT

BACKGROUND: Although environmental factors have been studied for their impact on mental health, the link between ambient temperature and mental disorders remains insufficiently explored.

AIM: This study aimed to explore the relationship between ambient temperature and the frequency of emergency psychiatric consultations at the sole university hospital in Paraguay from 2021 to 2023.

METHODS: This investigation adopted a quantitative, observational, cross-sectional design, using a case-crossover approach. Data collection entailed reviewing patient records and meteorological data, focusing on the daily mean temperatures and other meteorological variables. Statistical analysis was conducted using RStudio and SPSS, applying a distributed lag non-linear model (DLNM) for a seven-day lag period. Multinomial logistic regression was used to estimate odds ratios (ORs) for the likelihood of specific diagnoses resulting in emergency consultations in relation to temperature exposure.

RESULTS: The analysis covered 2,186 first-time emergency psychiatric consultations, with anxiety disorders being the most frequent diagnosis (24.3%), followed by depressive disorders (23.4%) and personality disorders (15.8%). Women accounted for 70.6% of all patients. The findings indicated that higher temperatures were associated with a greater frequency of consultations for certain disorders, including bipolar (OR up to 27.12 at Lag 1) and eating disorders (OR up to 100 at Lag 1). Conversely, a negative association was observed for schizophrenia, dissociative disorders, and trauma- and stressor-related disorders as temperature increased. Additionally, a linear relationship was found between lower relative humidity and increased number of consultations.

CONCLUSIONS: The findings underscore the impact of ambient temperature on psychiatric emergency consultations, revealing that the frequency of consultations for different conditions varies with temperature. These insights could inform public health strategies to mitigate the effects of climatic variation on mental health. These findings suggest the need for targeted mental health interventions to address vulnerabilities during periods of climatic stress, particularly in resource-limited settings.

PMID:40326281 | DOI:10.1177/00207640251336725

Pharm Biol. 2025 Apr 29;63(1):357-363. doi: 10.1080/13880209.2025.2499075. Epub 2025 May 6.

ABSTRACT

CONTEXT: As a naturally occurring terpenoid found in Cannabis sativa L. (Cannabaceae), cannabidiol (CBD) has gained public and industry interest for the purposes of personal well-being as a foodstuff and pharmaceutical. Despite a number of publications on CBD toxicology, many have significant limitations, especially those relating to genotoxicity. These include poor characterization of the CBD extract and/or lack rigor in conforming to accepted regulatory guidelines and best practice. A number of regulatory agencies have highlighted these issues and requested additional genotoxicity data to help ensure the safe use of CBD.

OBJECTIVE: To provide insights into the genotoxicity of a CBD isolate and its lipid carrier.

MATERIALS AND METHODS: We have conducted an in vitro mammalian cell micronucleus (OECD 487) and a bacterial reverse mutagenicity assay (Ames test) (OECD 471) in a CBD isolate (97% > CBD) with its carrier.

RESULTS: The samples tested were non-mutagenic, as determined in the Ames test. The in vitro micronucleus assay conducted was negative for genotoxicity, with no statistically significant increases in the incidences of micronucleated cells observed at any dose compared to negative controls.

CONCLUSIONS: These studies confirm that this CBD rich isolate in combination with its carrier, are unlikely to post any genotoxic hazard at exposure levels expected in foods.

PMID:40326262 | DOI:10.1080/13880209.2025.2499075

BJOG. 2025 May 6. doi: 10.1111/1471-0528.18190. Online ahead of print.

ABSTRACT

OBJECTIVE: Among women with uterine fibroids (UFs), we assess the extent to which the linzagolix effect on pain alleviation is explained by its effect on reducing heavy menstrual bleeding (HMB) and fibroid volume (FV).

DESIGN: Post hoc analysis on the pooled data from two randomised double-blind placebo-controlled phase 3 trials.

SETTING: 94 sites in the US (PRIMROSE 1 trial) and 95 sites in Europe/US (PRIMROSE 2 trial).

POPULATION: Women aged ≥ 18 years with ultrasound-confirmed UFs and HMB (n = 1012).

METHODS: Participants were randomised to linzagolix (100 mg and 200 mg, with and without hormonal add-back therapy) versus placebo. A post hoc mediation analysis was conducted on the pooled PRIMROSE 1 and PRIMROSE 2 data. The effect of linzagolix versus placebo on pain reduction was divided into three components (effect explained by HMB reduction associated with linzagolix, FV reduction associated with linzagolix, and remaining [not yet explained] treatment effect), with proportions of each component reported.

MAIN OUTCOME MEASURES: The mediation analysis outcome was clinically significant pain reduction, defined as a change of ≥ 2 pain categories from baseline to Week 24 using the Numeric Rating Scale (pain categories: no pain (0), and mild (1-3), moderate (4-6), severe pain (7-10)).

RESULTS: In the mediation analysis, 28%-51% (depending on treatment arm) of linzagolix effect on pain reduction was explained by its effect on HMB reduction, while 2%-8% was explained by its effect on FV reduction. The residual proportion ranged between 44% and 67%, depending on treatment arm, and was statistically significant only in the linzagolix 200 mg without add-back therapy arm (p = 0.002).

CONCLUSIONS: This analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200 mg alone) in linzagolix-treated women with UFs. Further research is needed to identify additional mediating factors.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT03070899 and NCT03070951.

PMID:40326221 | DOI:10.1111/1471-0528.18190

Adv Mater. 2025 May 6:e2502766. doi: 10.1002/adma.202502766. Online ahead of print.

ABSTRACT

To address the growing demand for energy and support the shift toward transportation electrification and intermittent renewable energy, there is an urgent need for low-cost, energy-dense electrical storage. Research on Li-ion electrode materials has predominantly focused on ordered materials with well-defined lithium diffusion channels, limiting cathode design to resource-constrained Ni- and Co-based oxides and lower-energy polyanion compounds. Recently, disordered rocksalts with lithium excess (DRX) have demonstrated high capacity and energy density when lithium excess and/or local ordering allow statistical percolation of lithium sites through the structure. This cation disorder can be induced by high temperature synthesis or mechanochemical synthesis methods for a broad range of compositions. DRX oxides and oxyfluorides containing Earth-abundant transition metals have been prepared using various synthesis routes, including solid-state, molten-salt, and sol-gel reactions. This review outlines DRX design principles and explains the effect of synthesis conditions on cation disorder and short-range cation ordering (SRO), which determines the cycling stability and rate capability. In addition, strategies to enhance Li transport and capacity retention with Mn-rich DRX possessing partial spinel-like ordering are discussed. Finally, the review considers the optimization of carbon and electrolyte in DRX materials and addresses key challenges and opportunities for commercializing DRX cathodes.

PMID:40326162 | DOI:10.1002/adma.202502766

J Texture Stud. 2025 Jun;56(3):e70019. doi: 10.1111/jtxs.70019.

ABSTRACT

This research focuses on the measurement of the modulus of elasticity as a key elasto-mechanical property for three Iranian rice varieties-Tarom Hashemi, Anbarbu, and Dom Siah-using macroscopic compression tests and Atomic Force Microscopy (AFM) at the microscopic scale. The results indicated that Anbarbu exhibited the highest modulus of elasticity, reaching 1656.940 MPa at the macroscopic level and 786.102 MPa at the microscopic level. These values represent measurements at different scales and should not be directly compared; instead, they reflect the structural resistance to deformation at each scale. Tarom Hashemi, in contrast, showed lower modulus values, with an average of 1466.263 MPa in macroscopic measurements and 697.630 MPa in microscopic measurements, indicating comparatively lower rigidity. The statistical t-test, conducted at a significance level of p < 0.05, confirmed significant differences between the macroscopic and microscopic measurements, emphasizing the importance of microscopic approaches for understanding detailed structural mechanics. These findings provide valuable insights for tailoring rice processing techniques by highlighting how the modulus of elasticity influences grain breakage and deformation, ultimately aiding in preserving grain quality during post-harvest handling and processing.

PMID:40326156 | DOI:10.1111/jtxs.70019

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Apr;33(2):557-564. doi: 10.19746/j.cnki.issn.1009-2137.2025.02.037.

ABSTRACT

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML).

METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed.

RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases).

CONCLUSION: Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.

PMID:40326134 | DOI:10.19746/j.cnki.issn.1009-2137.2025.02.037

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Apr;33(2):530-537. doi: 10.19746/j.cnki.issn.1009-2137.2025.02.033.

ABSTRACT

OBJECTIVE: To study the results, re-donation situation and characteristics of single-reagent reactive blood donors who were put into the reentry strategy in Wuhan area, explore the rationality and effectiveness of the current reentry strategy, and provide data support for the improvement of the reentry process of blood donors.

METHODS: From January 2020 to December 2023, blood donors who conform the reentry criteria and voluntarily applied for returning to Wuhan Blood Center were tested and the results were analyzed. According to the reentry strategy, serological testing and nucleic acid testing were carried out in parallel, serological testing was performed by ELISA with reagents from two different manufacturers, and the primary reactive samples were tested by double-well retest, and HBV/HCV/HIV nucleic acid detection was performed by RT-PCR with an individual donor test mode. Supplementary HBcAb testing was applied for HBV single reagent reactivity by chemiluminescence method. Supplementary TP-WB testing was applied for returning blood donors with repeated TP single reagent reactivity. If returning blood donors with HIV single reagent reactivity were repeated single reagent reactivity, the samples were sent to local CDC for confirmatory test.

RESULTS: 7 098 blood donors were qualified for reentry, 716 donors voluntarily applied for reentry, 436 donors successfully reentry, 251 donors entered the next round, 29 donors could not reentry. The reentry rates for the past four years were 66.67%（42/63）, 54.73%（81/148）, 60.71%（136/224） and 62.99%（177/281）, respectively. Up to December 31, 2023, 275 donors donated blood again, and the donation rates for past four years were 76.19%（32/42）, 72.84%（59/81）, 61.76%（84/136） and 56.50%（100/177）, respectively. After donating blood, 31 donors were disqualified again by blood screening and subjected to permanent deferral. The results of returning to the team had statistical differences in reentry items, educational level, age, and marriage（P < 0.05）.

CONCLUSION: The current reentry strategy adopted by the blood donation and supply institution can effectively retain part of blood donors, reduce the negative emotions of blood donors and increase blood resources.

PMID:40326130 | DOI:10.19746/j.cnki.issn.1009-2137.2025.02.033